Rhythms and blues: modulation of oscillatory synchrony and the mechanism of action of antidepressant treatments

Abstract

Treatments for major depressive disorder (MDD) act at different hierarchical levels of biological complexity, ranging from the individual synapse to the brain as a whole. Theories of antidepressant medication action traditionally have focused on the level of cell-to-cell interaction and synaptic neurotransmission. However, recent evidence suggests that modulation of synchronized electrical activity in neuronal networks is a common effect of antidepressant treatments, including not only medications, but also neuromodulatory treatments such as repetitive transcranial magnetic stimulation. Synchronization of oscillatory network activity in particular frequency bands has been proposed to underlie neurodevelopmental and learning processes, and also may be important in the mechanism of action of antidepressant treatments. Here, we review current research on the relationship between neuroplasticity and oscillatory synchrony, which suggests that oscillatory synchrony may help mediate neuroplastic changes related to neurodevelopment, learning, and memory, as well as medication and neuromodulatory treatment for MDD. We hypothesize that medication and neuromodulation treatments may have related effects on the rate and pattern of neuronal firing, and that these effects underlie antidepressant efficacy. Elucidating the mechanisms through which oscillatory synchrony may be related to neuroplasticity could lead to enhanced treatment strategies for MDD.

Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression

“…Local low-field stimulation may exert a therapeutic effect through resetting cortical oscillators [10,13], and evidence indicates that if low-field stimulation is delivered at the natural resonant frequency of a neuronal circuit, this stimulation may achieve therapeutic effect using low stimulation energy [22]. These results add to the growing body of literature suggesting that modulation of rhythmic oscillations in brain networks may be related to the mechanism of action of antidepressant treatments [45,46]. Future research should compare different energies of stimulation to determine if equal efficacy can be achieved with lower energy by taking advantage of the brain's resonant frequencies.…”

Quantitative Electroencephalographic Biomarkers in Preclinical and Human Studies of Huntington’s Disease: Are They Fit-for-Purpose for Treatment Development?

“…Hunter et al (45) examined the AP gradients of relative qEEG power and found two more potentially useful biomarkers in the alpha and delta frequency bands (45). The effect of HD disease progression on rhythmic oscillatory activity in the delta, theta, and alpha bands constitutes a highly plausible disease biomarker for increasing mHTT burden: oscillations in this frequency range are modulated by corticothalamic circuits (50, 51), and in particular, by thalamic nuclei that are known to show structural changes with disease progression (52, 53). Different thalamic nuclei regulate rhythmic oscillations in anterior and posterior brain regions, which could explain why the AP gradient would shift during disease progression as different thalamic nuclei become involved in the illness.…”

Imaging TMS: antidepressant mechanisms and treatment optimization

“…Cerebral blood flow change and functional connectivity have been found to correlate with power in the alpha band of the EEG and quantitative EEG methods have been developed to study connectivity (Leuchter, Cook, Hunter, Cai, & Horvath, 2012). It has been suggested that the changes in functional connectivity observed with BOLD may be generated by “entraining” cortico-cortical and cortical-subcortical networks to a frequency which helps to “reset” the oscillation frequency of the network and restore its normal function (Leuchter, Cook, Jin, & Phillips, 2013; Leuchter, Hunter, Krantz, & Cook, 2015b). Future studies of the mechanism of action should incorporate pre/post EEG to correlate BOLD findings with frequency entrainment.…”